It is proposed to further investigate the structure-function relationship of alpha-isopropylmalate synthase, the first specific enzyme in leucine biosynthesis. In particular, the isolation of a mutant hypersensitive to leucine will be attempted and the results obtained with the hypersensitive enzyme compared with those of normal and feedback-resistant enzyme. Also, the possible involvement of alpha-isopropylmalate synthase in repression of the leucine pathway will be studied. In other work, yeast alpha-isopropylmalate synthase will be purified and further characterized with respect to feedback inhibition, sensitivity to the CoA/acetyl-CoA ratio, and intracellular localization.